Molecular and cellular aspects of mental retardation in the Fragile X syndrome: from gene mutation/s to spine dysmorphogenesis.

Details

Serval ID
serval:BIB_58B23FA7A175
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Molecular and cellular aspects of mental retardation in the Fragile X syndrome: from gene mutation/s to spine dysmorphogenesis.
Journal
Advances in experimental medicine and biology
Author(s)
De Rubeis S., Fernández E., Buzzi A., Di Marino D., Bagni C.
ISSN
0065-2598 (Print)
ISSN-L
0065-2598
Publication state
Published
Issued date
2012
Volume
970
Pages
517-551
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
The Fragile X syndrome (FXS) is the most frequent form of inherited mental retardation and also considered a monogenic cause of Autism Spectrum Disorder. FXS symptoms include neurodevelopmental delay, anxiety, hyperactivity, and autistic-like behavior. The disease is due to mutations or loss of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein abundant in the brain and gonads, the two organs mainly affected in FXS patients. FMRP has multiple functions in RNA metabolism, including mRNA decay, dendritic targeting of mRNAs, and protein synthesis. In neurons lacking FMRP, a wide array of mRNAs encoding proteins involved in synaptic structure and function are altered. As a result of this complex dysregulation, in the absence of FMRP, spine morphology and functioning is impaired. Consistently, model organisms for the study of the syndrome recapitulate the phenotype observed in FXS patients, such as dendritic spine anomalies and defects in learning. Here, we review the fundamentals of genetic and clinical aspects of FXS, devoting a specific attention to ASD comorbidity and FXS-related diseases. We also review the current knowledge on FMRP functions through structural, molecular, and cellular findings. Finally, we discuss the neuroanatomical, electrophysiological, and behavioral defects caused by FMRP loss, as well as the current treatments able to partially revert some of the FXS abnormalities.

Keywords
Animals, Brain/metabolism, Brain/physiopathology, Child, Dendrites/metabolism, Dendrites/pathology, Disease Models, Animal, Drosophila melanogaster, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/drug therapy, Fragile X Syndrome/genetics, Fragile X Syndrome/metabolism, Fragile X Syndrome/physiopathology, Gene Expression, Gonads/metabolism, Gonads/physiopathology, Humans, Male, Mice, Molecular Targeted Therapy, Mutation, Phenotype, Protein Biosynthesis, RNA Stability, RNA, Messenger/genetics, Zebrafish
Pubmed
Create date
06/03/2017 17:23
Last modification date
20/08/2019 14:12
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